Cancer cells can change metabolic pathways, including glycolysis and glutamine metabolism, and produce the raw materials needed for rapid proliferation and survival. Therefore, research on metabolic pathways of cancer cells might help find the targets of cancer therapy. In this review, we outlined the metabolic features of aerobic glycolysis, glutamine metabolism and (tricarboxylic acid) TCA cycle in cancer. We also described metabolic targets for cancer therapy and therapeutic agents for the corresponding targets in these metabolic pathways, and finally discussed some of the challenges related to tumor metabolism as a therapeutic target in cancer therapy.

Objective To investigate the clinical features and genetic tests of a case with congenital muscular dystrophy type 1A (MDC1A). Methods Clinical data of proband were collected, and genetic change were tested using next generation sequencing, and literatures pertinent to the epidemiology, mechanisms, especially genetic testing of lisencephaly were reviewed. Results A 5 year and 2 month old boy present with normal intelligence and delayed motor development, he can be sit alone but not walk at two years old. Physical examination showed normal mental reaction, muscular dystrophy, hypotonia, and joint contracture at early age. From biochemical tests, we found creatine kinase (CK) and CK-MB were increased (491U/L, 41.8U/L). EMG test suggested possible muscle-derived damage. Brain MRI showed white matter abnormality. And a heterozygous mutation (c.2045-2046delAG) inherited from his mother in LAMA2 gene, and another novel heterozygous mutation (del Exon5) inherited from his father were identified by genetic test. Conclusions LAMA2 gene deficiency can lead to MDC1A, and gene testing can help diagnosis.

The urothelium is a transitional epithelium which lines on the renal pelvis, ureter, bladder and proximal urethra adjacent to the bladder. It’s a permeability barrier. In the process of urothelial development or injury repair, the mature urothelial cells expressing uroplakin appears after the hierarchical transcription of a series of transcription factors in basal stem cells. Understanding normal urothelial differentiation process of the urothelial cells could be beneficial to uncover the development of urothelial carcinoma so that to provide targeted therapy options and the study of the urinary tract repair process after injury. In addition, the study of stem cell differentiation microenvironment also provides important theoretical support for tissue engineering and tissue reconstruction. In this review, we discuss the latest findings on urothelial cell differentiation and its clinical significance.

Objective To investigate the analgesic effect and the safety assessment of intravenous injection of flurbiprofen axetil and sufentanil combined with epidural morphine for post-cesarean analgesia.Methods One hundred and eighty parturients (ASA Ⅰ-Ⅱ) undergoing elective cesarean section with combined spinal and epidural anesthesia were divided into morphine group (group A),sufentanil + morphine group(group B),flurbiprofen axetil+sufentanil+ morphine group(group C) with 60 cases in each group.All patients were used subarachnoid epidural anesthesia,at the end of the surgery,1.5 mg morphine diluted to 5 ml saline was injected into the epidural space of each patient.Additional,group B and group C received patient-controlled intravenous analgesia after cesarean section.Flurbiprofen axetil and sufentanil were diluted to 100 ml with saline.The visual analog scale (VAS) of rest and dynamic incisional pain and uterine contraction pain,Ramsay sedation scale (RSS),and adverse events were recorded at 6,12,24 h after operation.Results At 6,12,24 h after operation,the VAS scores of rest and dynamic incisional pain and uterine contraction pain in group B and group C were statistically lower than those in group A [rest incisional pain:(2.6 ± 0.6),(2.7 ± 0.4),(2.8 ± 0.3)scores in group A; (2.3 ± 0.3),(2.3 ± 0.4),(2.2 ± 0.3) scores in group B; (1.8 ± 0.4),(1.7 ±0.5),(1.9 ±0.4) scores in group C; dynamic incisional pain:(5.7 ±0.9),(5.5 ± 0.8),(5.6 ± 1.0) scores in group A; (3.8 ± 0.4),(3.7 ± 0.5),(3.7 ± 0.4) scores in group B ; (2.7 ± 0.4),(2.4 ± 0.5),(2.4 ± 0.6) scores in group C ; uterine contraction pain:(5.7 ± 1.2),(5.9 ± 0.9),(5.8 ± 1.1) scores in group A; (3.0 ± 0.5),(3.1 ± 0.6),(3.2 ± 0.7)scores in group B; (2.5 ± 0.5),(2.5 ± 0.6),(2.4 ± 0.4) scores in group C],and group C were lower than group B,and there were significant differences (P＜0.05).At 6,12,24 h after operation,Ramsay score in group B and group C was higher than that in group A [(1.8 ± 0.5),(1.7 ± 0.4),(1.9 ± 0.5) scores in group A; (3.4 ± 0.8),(3.2 ± 0.7),(3.3 ± 0.6) scores in group B; (2.7 ±0.7),(2.7 ±0.5),(2.6 ± 0.4)scores in group C],and group C was higher than group B,and there were significant differences (P ＜ 0.05).The incidence of adverse events in group A and group C was lower than group B [8.3％(5/60) and 23.3％(14/60) vs.40.0％(24/60)],and group A was lower than group C,and there were significant differences (P ＜ 0.05).Condusion Intravenous injection of flurbiprofen axetil and sufentanil combined with epidural morphine could perform better analgesic on postoperative incisional and uterine contraction pain after cesarean section and the incidence of adverse events is less than sufentanil combined with morphine.

0.05), there were significant statistic differences of any other two TI values (P0.05), there were significant statistic differences of any other two TI values (P0.05 ) , there were significant statistic differences of any other two TI values (P

Objective To investigate effects of neuromuscular electrical stimulation (NMES) on pulmonary arterial hypertension induced by chronic hypoxic hypercapnia in rats.Methods Eighteen male Sprague-Dawley rats were randomly divided into a normal control group (the control group),a hypoxic hypercapnia group (the model group),and a hypoxic hypercapnia + NMES group (the NMES group),each of 6.The rats in both the model and NMES groups were placed in an isobaric cabin with an O2 concentration of 9％ to 11％ and a CO2 concentration of 5％ to 6％ for 8 hours a day for 4 weeks.After leaving the cabin,NMES was performed on the NMES group's bilateral calf muscles for 30 minutes every day.The heart was removed,and the right ventricle (RV) and the left ventricle plus the septum (LV+S) were dissected.An index of right ventricular hypertrophy was calculated as RVHI=RV/(LV+S).Any changes in the pulmonary vasculature were observed using an optical microscope.WT％ and WA％ were calculated.The expression of hypoxia-inducible factor-1α (HIF-1α),PDH-E1α and PDK1 in the lung tissue were determined using western blotting.The LDH activity and the concentration of PDH in the lung tissue homogenate were measured was measured by spectrophotometric method using the LDH assay kit and ELISA,respectively.Results Compared with the control group,the average RVHI,WT％ and WA％,the protein expression of HIF-lα and PDK1,and LDH activity had all increased significantly in the NMES group,while the average expression of PDH-1Eα had decreased significantly.Compared with the model group,significant decrease was observed in the average RVHI,WT％,WA％,protein expression of HIF-1α and PDK1,and LDH activity in the NMES group,but the average expression of PDH-1Eα increased significantly.No significant differences in PDH concentration were detected among the 3 groups.Conclusions NMES may alleviate pulmonary artery hypertension induced by chronic hypoxic hypercapnia,at least in rats.The mechanism may be attributed to inhibiting the expression of HIF-1α protein,which may inhibit the activity of PDH-E1α and LDH,then the aerobic metabolism into glycolysis,finally improving the remodeling of the pulmonary vascular structure.

Objective To compare the MSCT findings of malignant focal pulmonary ground-glass opacity nodules (fGGO) and solid nodules of 3 cm or less, and try to find specific signs in fGGO. Methods Clinical data (sex ratio, age), size of lesion and MSCT findings (shape, margin, interface, internal characteristics, adjacent structure) of 105 cases pathologically confirmed to have solid lung cancers and 48 cases with fGGO less than 3 cm were retrospectively analyzed. Differences were analyzed by using the Fisher exact test or Mann-Whitney U test. Results The male and female ratio of solid lung cancer(60:45) were higher than that of fGGO (18:30, X~2 value 5.09, P<0.05). But no differences were found in age and size of lesion (P value 0.200,0.673). For solid lung cancer, the incidence of round shape (n=101), irregular (n=4), speculation (n=60), vacuole sign (n=12) and air bronchograms (n=0) were significantly different from those of fGGO (38, 10, 19,25 and 7, respectively), and the corresponding (X~2 values were 11.48,4.07,29.70 and 22.38 respectively, P<0.05). No differences were found in lobulation, cusp angle, spine-like process, well-defined, coarse, ill-defined interface, honey-combing, pleural indentation sign and blood vessel cluster sign (there are 85,0,33,5,100,0,0,59,35 cases for solid cancer, and 42,1,15,3,45,0,2,32,16 for fGGO (X~2 values 1.00,2.20, 0.00,0.15, 4.43,1.50, 0.00, P>0.05). Conclusions Malignant fGGO and solid lung cancer manifest mostly similar MSCT features. The frequency of irregular shape, vacuole sign and air bronchograms was higher in fGGO than in solid lung cancer to some degree, but speculation is more infrequent in fGGO, which may be attribute to thepathological type and basis of tumor.

Objective To evaluate the effect of dexmedetomidine on apoptosis in myocardial cells in rats with severe scald.Methods Eighteen healthy male Sprague-Dawley rats,weighing 220-280 g,were randomly divided into 3 groups (n =6 each) using a random number table:control group (group C),scald group (group B)and scald + dexmedetomidine 30 μg/kg group (group D).Thirty percent of the total body surface was shaved and then exposed to 94 ℃ water for 12 s.Rats were resuscitated with isotonic saline according to Parkland formula immediately after burn.Sham burn was produced in C group.In group D,the rats received inraperitoneal injection of dexmedetomidine 30 μg/kg immediately after burn,and the equal volume of normal saline was injected in group B.The left ventricle was removed at 12 h after burn to observe the pathological changes of myocardial tissues with light microscope and to detect the apoptosis in myocardial cells (TUNEL assay) and expression of glucose-regulated protein 78 (GRP78) and C/EBP-homologous protein (CHOP) (using Western blot).The apoptosis index was calculated.Results Compared with group C,the apoptosis index was significantly increased and the expression of GRP78 and CHOP was up-regulated in B and D groups (P ＜ 0.05).Compared with group B,the apoptosis index was significantly decreased and the expression of GRP78 and CHOP was down-regulated in group D (P ＜ 0.05).The pathological changes were obvious in group B and were significantly attenuated in group D.Conclusion Dexmedetomidine can protect myocardium through inhibiting endoplasmic reticulum stress-mediated apoptosis in myocardial cells in rats with severe scald.

Currently,revascularization is an effective rescue strategy for patients with acute myocardial infarc-tion.However,myocardial ischemia/reperfusion(I/R)injury induced by revascularization has become a significant risk factor affecting the long-term prognosis of patients with ischemic cardiomyopathy after revascularization,without precise treatment.Extracellular vehicles derived from mesenchymal stem cells are characterized by easy access,editability,and easy absorption of cells,and their application in treating myocardial I/R injury is considered valuable to study.This review focuses on the advances in research on mesenchymal stem cell-derived extracellular vehicles and their function of regulating myocardial I/R injury after natural drug intervention,hopefully offering ideas for the research of prevention and treatment of myocardial I/R injury.

Objective:1. To detect any change in the PTEN/Akt/FoxO1 signaling pathway in the muscles of rats with chronic hypoxia-hypercapnia treated using neuromuscular electrical stimulation (NMES), and 2. To document the role of chronic hypoxia-hypercapnia in inducing muscle atrophy.Methods:Thirty-two male Sprague-Dawley rats were randomly divided into a control group, a model group, a mock stimulation group, and an NMES group, each of eight. All of the rats in the model group, the mock stimulation group and the NMES group were placed in a hypoxia-hypercapnia chamber with a 9-11% O 2 and 5.5-6.5% CO 2 atmosphere for 8h per day and 7d per week, lasting 4 weeks. The control group were placed in a similar chamber with normal air. In the last 2 weeks, after the 8h in the chamber, the NMES group were given 30min of electrical stimulation at 100Hz to the calf muscles of their bound lower limbs. The mock stimulation group were only bound without any electrical stimulation. After the 4-week intervention, the gastrocnemius muscles were resected and their cross-sectional areas (CSAs) were observed using hematoxylin-eosin staining. Immunohistochemistry and western blotting were employed to detect the protein expression of phosphatase and tensin (PTEN), p-Akt, Akt and FoxO1. Results:Compared with the control group, a significant decrease was observed in the average CSA and in the expression of p-Akt and Akt in the model group, while a significant increase was found in the average protein expression of PTEN and FoxO1. Compared with the model group, there was a significant increase in the average CSA, as well as the average expression of p-Akt and Akt in the NMES group, but a significant decrease in the average expression of PTEN and FoxO1.Conclusion:Neuromuscular electrical stimulation can relieve muscle atrophy from chronic hypoxia-hypercapnia by inducing skeletal muscle protein synthesis through regulating the PTEN/Akt/FoxO1 signaling pathway, at least in rats.